5-HT6 receptor is one of the potential therapeutic target for the development of cognitive enhancers. 5-HT6 receptor is localized exclusively in central nervous system, in areas important for learning and memory. In recent years several studies have shown that 5-HT6 receptor antagonists show beneficial effect on cognition in several animal models. Several 5-HT6 antagonists advanced into clinic.
1-[(2-Bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole. Dimesylate monohydrate is a promising pharmaceutical agent, which is a selective 5-HT6 receptor antagonist intended for the symptomatic treatment of Alzheimer's disease and other disorders of memory and cognition like Attention deficient hyperactivity, Parkinson's and Schizophrenia.
Currently 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazin-1-yl)methyl]-1H-indole dimesylate monohydrate is undergoing clinical trials designed to confirm its efficacy. The demand for 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate as a drug substance has increased substantially with the advent of its clinical testing. The future need for much larger amounts is projected due to the intended commercialization of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate mono hydrate.
For the person skilled in art, it is a well known fact that various parameters will change during the manufacture of a compound on a large scale when compared to the synthetic procedures followed in laboratory. Therefore, there is need to establish and optimize large scale manufacturing process. 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole and it's pharmaceutically acceptable salts and their syntheses were disclosed by Ramakrishna et al. in WO 2004/048330. The process for the preparation of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate disclosed herein was proved to be unsatisfactory for adaptation to the large scale manufacturing. Hence it became highly desirable to establish the manufacturing process of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate. Therefore, we established and optimized the manufacturing process of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate, monohydrate, which is amenable to large scale synthesis of 1-[(2-bromophenyl)sulfonyl]-5-methoxy-3-[(4-methyl-1-piperazinyl)methyl]-1H-indole dimesylate monohydrate.